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Behcet’s disease in Budd-Chiari syndrome
Anne Claire Desbois, Pierre Emmanuel Rautou, Lucie Biard, Nadia
Belmatoug, Bertrand Wechsler, Mathieu Resche-Rigon, Virginie Zarrouk,
Bruno Fantin, M Pineton de Chambrun, Patrice Cacoub, et al.
To cite this version:
Anne Claire Desbois, Pierre Emmanuel Rautou, Lucie Biard, Nadia Belmatoug, Bertrand Wechsler, et
al.. Behcet’s disease in Budd-Chiari syndrome. Orphanet Journal of Rare Diseases, BioMed Central,
2014, 9, pp.104. �10.1186/s13023-014-0153-1�. �hal-01334624�
R E S E A R C H A R T I C L E
Open Access
Behcet
’s disease in budd-chiari syndrome
Anne Claire Desbois
1,2*, Pierre Emmanuel Rautou
3, Lucie Biard
5, Nadia Belmatoug
4, Bertrand Wechsler
1,
Mathieu Resche-Rigon
5, Virginie Zarrouk
4, Bruno Fantin
4, M Pineton de Chambrun
1, Patrice Cacoub
1,2,6,
Dominique Valla
3, David Saadoun
1,2,6and Aurélie Plessier
3Abstract
Background: Behcet’s disease (BD) is a well-known cause of Budd-Chiari syndrome (BCS). Data are lacking on the presentation and outcome of BCS related to BD.
Methods: We investigated the relationship between BD and BCS in 14 patients with both diseases and compared the results to 92 BCS patients without BD.
Results: Male gender (p = 0.003), North African origin (P = 0.007) and inferior vena cava obstruction (P < 0.0001) were more frequent in patients with BD and BCS than in those with BCS alone and the plasma C-reactive protein level was higher (p = 0.003). Two of the patients with the combined diseases underwent recanalization of the vena cava and the hepatic veins, none received transjugular intrahepatic portosystemic shunts (TIPS), one received a surgical shunt and one underwent liver transplantation. TIPS were less frequent in patients with BD and BCS than in those with BCS alone (P = 0.019). Eighty six per cent of patients with BCS and BD received corticosteroids and immunosuppressive therapy. The 5-year transplantation-free survival rate was 63% in patients with BCS alone and 91% in those without BD (P = 0.11). In our series and in the literature, a high number of patients [12 (61.5%) and 11 (64.7%) respectively] treated with anticoagulation and corticosteroids and/or immunosuppressants did not require invasive treatment.
Conclusion: This study shows a higher frequency of IVC obstruction in patients with BCS and BD. Medical treatment with anticoagulation and immunosuppressive agents may improve the symptoms of BCS. Therefore early management with immunosuppressive and anticoagulation therapy appears to be the treatment of choice in patients with BCS and BD.
Keywords: Budd-chiari syndrome, Hepatic vein thrombosis, Behcet’s disease, Immunousuppressive agents Background
Budd Chiari Syndrome (BCS) is related to an obstruc-tion of the hepatic venous outflow tract at the hepatic veins or the inferior vena cava (IVC). This condition is associated with a high risk of complications and death due to portal hypertension and liver failure. Most cases of BCS are related to thrombosis resulting from one or several prothrombotic conditions [1]. Myeloproliferative disorders are associated in approximately 50% of cases, and represent the leading cause of primary BCS. Other
acquired [e.g. antiphospholipid syndrome (about 10%) or paroxysmal nocturnal hemoglobinuria (about 2%)] and inherited conditions are the cause in a smaller proportion of BCS. Behcet’s disease (BD) is found in approximately 5% of patients with BCS in western countries [1]. BD was reported in 9% of BCS patients in Turkey, making it the third cause of the disease in that country [2], and 13% of patients in Egypt [3].
BD is a chronic and relapsing vasculitis characterized by oral and genital aphtosis, ocular inflammation as well as cutaneous, vascular and nervous system manifestations [4]. Vasculitis is the main pathological finding of BD, and all sized vessels can be involved in the arterial and venous systems [5-7], although venous involvement is more fre-quent than arterial. In a recent survey, 37% of BD patients had venous thrombosis, and BCS occurred in 2.4% of these cases [8]. BCS is the most severe venous manifestation of * Correspondence:anneclairedesbois@yahoo.fr
1Department of Internal Medicine and clinical Immunology APHP, Paris
France, Centre de référence des maladies autoimmunes et systémiques rares, Université Pierre et Marie Curie, Paris 6, Paris, France
2
Laboratory I3“Immunology, Immunopathology, Immunotherapy”, UMR CNRS 7211, INSERM U959, Groupe Hospitalier Pitié-Salpetrière, DHU I2B Inflammation, Immunopathology, Biotherapy, Université Pierre et Marie Curie, Paris 6, Paris, France
Full list of author information is available at the end of the article
© 2014 Desbois et al; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
BD and is associated with a 9 fold-increase in mortality in these patients [8].
Because BD and BCS are uncommon, data on BCS re-lated to BD are limited to small retrospective series or single case reports. Thus data on the clinical features and the outcome and management of patients with BCS and BD are lacking. The present study retrospectively compared 14 patients with both diseases to 92 patients with BCS without BD.
Methods
Patients
The characteristics of 14 consecutive BCS patients with BD diagnosed between 1995 and 2012 were compared to those of a previously reported cohort of 92 BCS patients without BD, diagnosed between 1995 and 2005 [9]. All fourteen patients with BCS and BD met the ICBD cri-teria for BD [4]. BD patients were followed in both de-partments [the department of internal medicine at Hôpital Pitié-Salpêtrière (Paris, France) and the liver unit at Hôpital Beaujon (Clichy, France) for BCS manage-ment]. The patients with BCS without BD were followed at the Hepatology Department of the Hôpital Beaujon. The diagnosis of BCS was based on confirmation of hep-atic venous outflow tract obstruction based on imaging data: venous Doppler ultrasound, CT angiography and/ or magnetic resonance angiography (MRA).
Venous outflow obstruction due to right-sided heart failure and sinusoidal obstruction syndrome were not included.
Data on demographic characteristics were collected dur-ing the study period (gender, age and geographic origin), clinical presentation of BCS (date of BCS, main symptoms, number of occluded veins), risk factors for thrombosis [proteins C, S and antithrombin III deficiency R506Q mu-tation of factor V, G20210A mumu-tation of prothrombin and C677T mutation of methylene-tetrahydrofolate-reductase (MTHFR) gene, plasma homocysteine level, anticardiolipin and anti-β2Gp1 antibodies, tests for paroxysmal nocturnal hemoglobinuria and JAK2 V617F mutation] and labora-tory findings (liver enzymes, serum creatinine, prothrom-bin time) and imaging features. Search for signs of BD were recommended as part of the routine work-up. Treat-ment and overall survival was recorded for each patient. The Rotterdam prognostic score was calculated according to Murad et al. [10].
Statistical analysis
Patient characteristics and survival were compared be-tween BCS patients with and without BD. Quantitative variables are reported as medians and ranges and were compared by the Wilcoxon rank-sum test. Categorical variables were described with counts and percentages and were compared by the Fisher’s exact test. Overall
survival was defined as the time between the date of diagnosis of BCS and death. Living patients were cen-sored at the date of the last recorded follow-up visit. Overall survival was estimated using the Kaplan Meier estimator and compared between groups by the log rank test. The probability of survival was presented as a percent and a 95% confidence interval. All tests were two-sided andP-values ≤0.05 were considered to be sig-nificant. Analyses were performed using the R statistical software version 2.14.0 (available online at http://www. R-project.org).
Review of the literature
We systematically reviewed the medical literature via PubMed using the following keywords: “Budd-Chiari Syndrome”, “Behcet’s disease” and “hepatic vein occlu-sion”. We only analyzed cases reports and series pub-lished after 1980 in English or in French.
Results
Baseline characteristics
Baseline characteristics of the 106 patients with BCS with and without BD are summarized in Table 1. Four-teen BCS patients also had BD. The median age at diag-nosis of BCS was 33 years old (range 22–45) and 79% were men. Male gender (p = 0.003) and North African origin (p = 0.007) were more frequent in patients with BCS and BD than in those without BD (n = 92).
Four (28.6%) patients had already been diagnosed with BD when BCS was diagnosed [median time 11 months (range 3–97 months)]. The diagnosis of BD was con-comitant with the diagnosis of BCS in 8 (57%) patients. In the remaining 2 patients, BD was diagnosed 14 and 30 months after BCS, respectively. Major organ or tissue involvement of BD included oral (100%) and genital mu-cosa (64%), eyes (29%), joints (29%), nervous system (21%), arterial bed (29%) and heart (50%).
Ascites and splenomegaly were less common in BCS pa-tients with BD than in those without (Table 1). Median C-reactive protein (CRP) levels at the diagnosis of BCS were higher in BD patients than in those without. Laboratory results were similar in both groups, except for a lower serum bilirubin level in BD patients. IVC obstruction (suprahepatic and infrahepatic IVC occlusions) at pres-entation was almost 4 times more common in BD pa-tients with BCS than in those without BD. Most (n =11, 79%) patients with BCS and BD had other types of ven-ous thrombosis as described in Table 2. Most of these thromboses were diagnosed at the same time as BCS in BD patients. Five patients (36%) with BCS and BD had an associated prothrombotic condition (Table 2). Three out of 14 BD patients [21.4%, 95% CI (7.1; 48.5)] were HLA B51 positive.
Treatments of BCS in BD patients
The main features of BCS related treatment are indi-cated in Table 3 and Figure 1. Treatment included anticoagulation with heparin followed by a coumarine derivative in all cases. None of the BCS patients with BD received transjugular intrahepatic portosystemic shunts (TIPS) and one underwent liver transplantation. Patients with BCS and BD received TIPS less frequently and vena cava thrombolysis more often than those without BD (Table 3). The reason that TIPS were not used included a good response to medical therapy in 11
patients with BCS, or a contraindication due to associ-ated IVC obstruction in 3.
Complications of anticoagulation included epistaxis and hematuria in 1 patient.
Treatment of BD
Specific treatment for BD is presented in Figure 1. Twelve (86%) patients with BCS and BD received corti-costeroids (0.5-1 mg/kg/day of oral prednisone in 12 pa-tients including pulses of 1 g methylprednisolone for 3 days in 2 cases). Twelve (86%) patients received
Table 1 Baseline characteristics of BCS patients with and without BD
BCS with BD (n =14) BCS without BD (n =92) p Age at BCS diagnosis, median (range) 33 (22–45) 38 (16–77) 0.086 Male gender, n (%) 11/14 (79%) 32/92 (35%) 0.003
Geographic origin 0.0002
Europe 6 (43%) 66 (73%)
North Africa 8 (57%) 12 (13%)
Type of outflow obstruction
IVC occlusion, n (%) 10/14 (71%) 16/91 (18%) < 0.0001 HV occlusion alone, n (%) 4/11 (36%) 75/91 (82%) 0.002 Combined HV and IVC occlusion, n (%) 6/11 (55%) 15/91 (16%) 0.009 Number of hepatic veins thrombosed, median ± SD 2 3 0.017 1 HV thrombosed, n (%) 3/10 (30%) 5/91 (5%)
2 HV thrombosed, n (%) 1/10 (10%) 13/91 (14%) 3 HV thrombosed, n (%) 5/10 (50%) 72/91 (79%) Clinical features at baselinea, n (%)
Ascites 6/13 (46%) 72/92 (78%) 0.036 Hepatomegaly 6/13 (50%) 55/92 (60%) 0.38 Splenomegaly 2/12 (17%) 51/92 (55%) 0.014 Abdominal pain 6/13 (46%) 62/92 (67%) 0.21 Hepatic encephalopathy 0/13 7/90 (8%) 0.59 Gastrointestinal bleeding 0/13 10/92 (11%) 0.36 Laboratory at baselinea ALT < 5 × ULN, n (%) 10/11 (91%) 60/92 (65%) 0.10 AST < 5 × ULN, n (%) 10/11 (91%) 63/92 (68%) 0.17 Bilirubinemia (μmol/l), med(min-max) 13 (6–38) 31 (7– 207) < 0.0001 Albuminemia (g/l), med(min-max) 37(26–49) 35(19–52) 0.94 CRP level (mg/L), med(min-max) 85(7–238) 16(3–344) 0.003 Creatinemia (μmol/L), med(min-max) 80(44–120) 73(36–428) 0.34 Prothrombin Time < 70%, n (%) 5/11 (45.5%) 62/92 (67.4) 0.19 Thrombopenia (< 150.10 [9]/L), n (%) 2/12 (16.7%) 18/92 (19.6%) 1 Rotterdam BCS index 1 (0.0;1.2) 1.2 (0.0;3.9) 0.0007 Abbreviations: ALT Alanine aminotransferase, AST Aspartate aminotransferase, BD Behcet’s disease, BCS Budd-Chiari Syndrome, CRP C reactive protein, HV Hepatic vein, IVC Inferior vena cava, Med Median, ULN Upper limit of normal.
a
In BD patients, laboratory values at baseline were available in 11 patients for AST, ALT, creatinemia and CRP level, in 10 patients for albuminemia and in 12 patients for biliburinemia.
In BCS patients without BD, laboratory values were available in 90 patients for bilirubinemia, in 73 patients for albuminemia, in 87 patients for creatinemia and 41 patients for CRP level.
immunosuppressive therapy including azathioprine (2– 3 mg/kg/day, n = 9), cyclophosphamide (pulses of 750 mg/ m [2] /4 weeks during 6–12 months, n = 4), oral cyclospor-ine (3 mg/kg/day, n = 1). One patient received anti-tumor necrosis factor-α (anti-TNFα) inhibitor (infliximab 5 mg/kg intravenously at week 0, 2, 6 and every 6 to 8 weeks, n = 1). Three patients received 2 immunosuppressive and/ or biologic agents [cyclophosphamide followed by azathio-prine (n = 1) or cyclosporine (n = 1) and infliximab followed by azathioprine (n = 1)].
Two (15.4%) of the 13 patients who received anti-coagulation and corticosteroids and/or immunosup-pressants died; immunosuppressive therapy was started more than 2 years after the diagnosis of BCS in 1 of these. Eight (61.5%) of these 13 patients did not require endovascular treatment or surgery. The 5 other patients required additive invasive treatments [thrombolysis (n = 3), additional stent (n = 1) and surgical decom-pression by mesoatrial shunting (n = 1)]. This last pa-tient was still alive after surgery at the end of follow up but had refractory ascites.
The patient who received only anticoagulation had a favourable outcome.
The main complications of immunosuppressive agents included adenitis with azathioprine (n = 1), zoster infec-tion with anti-TNF alpha therapy (n = 1) and pancytopenia under azathioprine (n = 1).
Survival
Median follow-up for the study group (n = 106) was 54 months (range 1–142 months). Mortality in BCS pa-tients with BD was 14.3% after a median follow up of 53 months. One and 5-year overall survival rates were 84% (CI 95% 77–92) and 79% (CI 95% 71–88) respect-ively in BCS patients without BD; and 100% and 91% (CI 95% 75–100) respectively in BCS patients with BD (no significant difference) (Figures 2a and b). Transplant-ation free survival rates in BCS patients with and with-out BD, were 100% and 77% (CI 95% 68–86) at 1 year, and 91% (CI 95% 75–100) and 63% (CI 95% 53–75) at 5 years, respectively.
Death was related to liver disease in the 2 patients with BD who died.
Literature review
Out of the 95 BD patients with BCS reported in litera-ture, the 61 from publications in English and French were included in the study [11-32]. Data were obtained from 19 case-reports including fewer than 5 patients) and 3 series (including more than 5 consecutive pa-tients). Ninety percent of the patients were men. Median age was 26 years old (range 12–58). All patients were symptomatic. Ninety eight percent of the patients had ascites, 74% hepatomegaly, 26% splenomegaly, 23% ab-dominal pain, 16% jaundice and 13% hepatic encephal-opathy. Most patients had elevated liver enzymes. The mean serum bilirubin level was 79 μmol/L, and the mean prothrombin time ratio was 49%. Ninety one per-cent of the patients had associated IVC thrombosis. Lower limb thrombosis, intracardiac thrombosis, pul-monary embolism and renal vein thrombosis were asso-ciated with BCS in 28, 22, 13 and 9% of the patients, respectively.
Table 2 Disease characteristics of patients with BD and BCS
Patients with BD and BCS (n = 14)
Additional etiologic factors, n (%) 5 (38.5%) Antiphospholipid antibodies 2 Hyperhomocyteinemia 2 Factor II heterozygous gene mutation 1 Associated venous thrombosis, n (%)
Pulmonary embolism 7 (50%) Intracardiac [right atrium/right ventricle] 5 (36%) [29%/7%] Superior vena cava 3 (21%) Lower limbs 4 (29%) Cerebral 1 (7%) Abbreviations: BCS Budd-Chiari Syndrome, BD Behcet’s disease.
Table 3 Main treatments of BCS patients with and without BD
BCS with BD (n =14) BCS without BD (n =92) p Anticoagulation, n (%) 14 (100%) 92 (100%) 1.00 Endovascular treatment, n (%) 2 (14%) 17 (18%) 1.00 Thrombolysis, n (%) 3 (21%) 1 (1%) 0.007 TIPS, n (%) 0 (0%) 28 (30%) 0.019 Surgical decompressiona, n (%) 1 (8%) 7 (8%) 1.00 OLT, n (%) 1 (7%) 15 (16.3%) 0.69
Abbreviations: BCS Budd-Chiari Syndrome, BD Behcet’s disease, TIPS Transjugular intrahepatic portosystemic shunt, OLT Orthotopic liver transplantation.
a
Data on surgical decompression was available for 13 patients in BCS patients with BD. Bold indicates significant differences.
Treatment and outcome were available in 32/61 pa-tients with BCS and BD reported in literature. Data are summarized in Table 4. After a mean follow-up of 30 months, 19 (59%) patients improved, 11 (34%) died, 1 relapsed and 1 had persistent ascites. Two (12%) of the 17 patients treated with anticoagulation, corticosteroids and/or immunosuppressive agents, died (despite surgical decompression in one), 11 (65%) improved without re-ceiving endovascular/surgical treatment, 2 improved after surgical or endovascular treatment, 1 had persistent ascites and 1 relapsed 5 years after surgery. Four (67%) of the 6 patients treated with corticosteroids with or without immunosuppressants and without anticoagula-tion died and 2 had a favourable outcome. Three of the 5 patients (60%) treated with anticoagulation only died (despite surgical decompression in one case) and 2 were still alive in good physical condition after thrombectomy in one [14]. Two of the 4 patients who did not receive anticoagulation, corticosteroids or immunosuppressive agents died (including one after thrombectomy) and the
remaining 2 cases improved [after intravenous throm-bolysis (n = 1) and with aspirin and colchicine (n = 1)] [11].
Discussion
This study reports the largest series of consecutive pa-tients with BCS and underlying BD. Most previous stud-ies of this rare combination of disorders have consisted of case reports and therefore little is still known about the specific clinical features, treatment outcome or prog-nosis. In the current study, we compared the course of the disease in 14 patients with BCS and BD to a cohort of patients with BCS in whom BD was excluded as the underlying cause. Previous surveys indicate that BD may be responsible for up to 13% of the cases of BCS [1-3].
The results of this study confirm and expand those from previous smaller studies [3,17] on baseline charac-teristics of patients at diagnosis of BCS. The main clin-ical features at diagnosis of BCS that differed between patients with and without BD were a younger age, a
significant predominance of men, a North African origin and a higher frequency of associated thrombosis in other territories, as expected for BD patients in general. These findings are similar to the data from Bismuth et al. who reported male predominance (male/female ratio, 19:1) in BCS patients with BD compared to those without (i.e. mainly patients with myeloproliferative disorders) [17].
Our study reported a 4-fold higher prevalence of IVC thrombosis in patients with than in those without BD. This emphasizes the significant association between BCS and IVC occlusion in patients with BD. Thus, the pres-ence of IVC thrombosis in patients with BCS should suggest BD, which should then be investigated. Indeed, the diagnosis of BD had not yet been made in 2/3 of BCS patients with BD when BCS occurred. In our study, most of patients with BCS and BD had thrombosis in other territories (i.e. pulmonary artery, intracardiac, su-perior vena cava) which might be a useful indication to suggest and search for BD.
Despite a higher frequency of associated IVC throm-bosis, the short-term prognosis of BCS patients with BD did not differ from that in BCS patients without BD. The presence of associated IVC thrombosis in BD pa-tients and the favourable outcome under immunosup-pressants explain in part the low frequency of TIPS. Bayraktar et al. [22] observed a better outcome in BD patients with BCS without IVC thrombosis (100% sur-vival in 2 patients) while the mortality was 66% in pa-tients with BCS and IVC thrombosis (n = 8) . In our
cohort, none of the 4 patients with BCS and BD without IVC obstruction died. However, in recent surveys on BCS from all causes, IVC obstruction was not found to be associated with death or an intervention in multivari-ate analysis [33-35].
Early diagnosis of BD is necessary in BCS patients to begin early and specific treatment for BD. Indeed in the present study and in the literature, pharmacological antic-oagulation and immunosuppression alone were associated with favourable outcomes in patients with BCS and BD. However, it is important to remember that results in the literature are retrospective and include mainly case-reports, which may cause a significant reporting bias. Moreover, differences with our cohort might also be caused by less uniform management in case-reports. In our survey, the mortality rate in patients treated with anticoagulation and corticosteroids and/or immunosup-pressants was 18%. In the literature, the mortality rate in patients with similar treatment was 12% but was 60% in patients treated with anticoagulation only. In our cohort, 8 (62%) patients had a favourable outcome with medical therapy alone (i.e. anticoagulation and immunosuppressive agents and/or corticosteroids) and without endovascular treatment or surgery. In contrast in a large series of BCS from all causes, only 20-49% of patients treated with anticoagulation alone without invasive treatment had a favourable outcome [36,37].
The pathogenesis of thrombosis in BD is not fully understood. Thus far no consistent primary coagulation
Figure 2 Overall survival in BCS patients with (n = 14) and without (n = 92) BD (a); Transplantation free survival in BCS patients with (n = 14) and without (n = 92) BD (b).
or fibrinolytic system abnormalities have been identified in BD [38,39]. Because venous inflammation is probably the cause of deep vein thrombosis in patients with BD [40], an immunosuppressive approach to management seems reasonable, although no large randomized con-trolled trials have directly addressed this issue. In a pre-vious study on venous thrombosis in BD, we showed that immunosuppressive agents significantly improved the prognosis by decreasing the relapse of thrombosis by four fold [8]. Another retrospective survey in 37 BD pa-tients with venous thrombosis compared immunosup-pressive, anticoagulation treatment and a combination of immunosuppressants and anticoagulants [41]. Thrombosis recurred in three of the four patients in the anticoagulant
treatment group (75%) compared to 2/16 cases (12.5%) in the immunosuppressant group and to 1/17 cases (5.9%) in the combination group.
The limitations of the present study due to the rarity of both conditions must be kept in mind. This was a retrospective analysis and we could not collect complete longitudinal data in patients who were only seen inter-mittently. Moreover, the studies in the literature are mainly case-reports with a potential selection bias. Nevertheless, this study indicates that (a) most BCS pa-tients with BD present with IVC involvement and other venous thrombosis and (b) TIPS are rarely used (c) des-pite this, the overall outcome in patients with BD is not different from that in patients with BCS without BD and
Table 4 Treatments and outcome of the 61 BD patients with BCS reported in literature
Date of publication/authors Number of patients Anti-coagulation Cortico-steroids Immuno-suppressive therapy Surgery Endovascular treatment Outcome Follow up (months) 1980/ [11] 1 0 0 0 0 0 death 4
1996/ [20] 1 0 0 0 1(thrombectomy) 0 death During surgery
2000/ [23] 1 0 0 0 0 0 favourable 180
1983/ [13] 1 T 0 0 0 0 favourable 72
No treatment 4 0 (T, n =1) 0 0 1 thrombectomy 0 Death n = 2 (50%)
1985/ [14] 1 0 1 1 0 0 favourable 24 2002/ [24] 1 0 1 1 0 0 death 3 2007/ [28] 1 0 1 0 0 thrombolysis (failure) death ND 2007/ [29] 3 0 3 3 0 0 death (n = 2) favourable (n = 1) 7;7;6 No ATCG 6 0 6 5 0 0 Death n = 4 (67%) 1983/ [12] 1 1 0 0 1(shunt) 0 death 1 1986/ [15] 1 1 0 0 0 1 (stent) favourable 36 1991/ [18] 1 1 0 0 0 0 death 1.25 1990/ [17] 1 1 0 0 0 0 favourable 24 2008/ [30] 1 1 0 0 0 0 death ND
ATCG alone 5 5 0 0 1 1 Death n = 3 (60%)
1990/ [17] 3 3 (T, n = 1) 2 1 2 (shunt) 0 death (n = 1) 30;4;4 2002/ [25] 1 1 1 0 1 0 relapse (n = 1) 60 2004/ [26] 1 1 1 1 0 dilatation and stent favourable 0.25 2007/ [27] 4 4 4 4 0 0 death (n = 1) 1;96;48;36 2008/ [30] 6 6 6 2 0 0 favourable (n = 6) 43 2011/ [31] 1 1 1 1 0 0 favourable 1 2011/ [32] 1 1 1 1 0 0 alive 1.5
ATCG and IS 17 17 16 10 3 1 Death n = 2 (12%)
TOTAL 32 ATC 22 (69%) 22 (69%) 15 (47%) 5 (16%) 3 (9%) 12 (38%) 29.7 months Thrombolysis
2 (6%)
(d) the association of immune suppression to anticoagu-lation in medical therapy has a specific impact on BCS in BD patients. Therefore, early combination immuno-suppressants and anticoagulation therapy (with caval recanalisation procedures when appropriate), appears to be the treatment of choice in patients with BCS and BD.
Abbreviations
BCS:Budd-chiari syndrome; IVC: Inferior vena cava; BD: Behcet’s disease; MRA: Magnetic resonance angiography; MTHR: Methylene-tetrahydrofolate-reductase; TIPS: Transjugular intrahepatic portosystemic shunt; CRP: C-reactive protein; ALT: Alanine aminotransferase; AST: Aspartate aminotransferase. Competing interest
The authors do not have any competing interest to declare. Authors’ contributions
All the authors have contributed to the work and have approved the manuscript. AC Desbois and PE Rautou have collected, interpreted data and have contributed to draft the manuscript, M Pineton de Chambrun has collected data, L Biard and M Resche-Rigon have interpreted data, N Belmatoug, B Wechsler, V Zarrouk, B Fantin, P Cacoub have contributed to draft the manuscript and DC Valla, D Saadoun and A Plessier have interpreted data and have contributed to draft the manuscript. Authors’ information
D Saadoun and A Plessier are co-senior of the article. Author details
1Department of Internal Medicine and clinical Immunology APHP, Paris
France, Centre de référence des maladies autoimmunes et systémiques rares, Université Pierre et Marie Curie, Paris 6, Paris, France.2Laboratory I3
“Immunology, Immunopathology, Immunotherapy”, UMR CNRS 7211, INSERM U959, Groupe Hospitalier Pitié-Salpetrière, DHU I2B Inflammation,
Immunopathology, Biotherapy, Université Pierre et Marie Curie, Paris 6, Paris, France.3Department of Hepatology; Hôpital Beaujon, INSERM U773, Service
d’hépatologie, 100 boulevard du Général Leclerc, 92118 Clichy cedex, France.
4Department of Internal Medicine, Hôpital Beaujon, Clichy, France. 5
Department of Biostatistics and Medical Data Processing; INSERM U717, Hôpital Saint-Louis, Paris, France.6Université Pierre et Marie Curie-Paris 6,
Paris, F-75013 France; AP-HP, Hôpital Pitié-Salpêtrière, Service de Médecine Interne et d’Immunologie clinique, F-75013 Paris, France.
Received: 24 March 2014 Accepted: 27 June 2014
References
1. Valla D-C: Primary budd-chiari syndrome. J Hepatol 2009, 50(1):195–203. 2. Uskudar O, Akdogan M, Sasmaz N, Yilmaz S, Tola M, Sahin B: Etiology and
portal vein thrombosis in budd-chiari syndrome. World J Gastroenterol 2008, 14(18):2858–2862.
3. Sakr M, Barakat E, Abdelhakam S, Dabbous H, Yousuf S, Shaker M, Eldorry A: Epidemiological aspects of budd-chiari in Egyptian patients: a single-center study. World J Gastroenterol 2011, 17(42):4704–4710.
4. International Team for the Revision of the International Criteria for Behçet’s Disease (ITR-ICBD): The international criteria for Behçet’s disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria. J Eur Acad Dermatol Venereol 2014, 28(3):338–347. 5. Calamia KT, Schirmer M, Melikoglu M: Major vessel involvement in behçet
disease. Curr Opin Rheumatol 2005, 17(1):1–8.
6. Koç Y, Güllü I, Akpek G, Akpolat T, Kansu E, Kiraz S, Batman F, Kansu T, Balkanci F, Akkaya S: Vascular involvement in Behçet’s disease. J Rheumatol 1992, 19(3):402–410.
7. Sarica-Kucukoglu R, Akdag-Kose A, KayabalI M, Yazganoglu K, Disci R, Erzengin D, Azizlerli G: Vascular involvement in Behçet’s disease: a retrospective analysis of 2319 cases. Int J Dermatol 2006, 45(8):919–921. 8. Desbois AC, Wechsler B, Resche-Rigon M, Piette JC, Huong D, Amoura Z, Koskas F, Desseaux K, Cacoub P, Saadoun D: Immunosuppressants reduce venous thrombosis relapse in Behçet’s disease. Arthritis Rheum 2012, 64(8):2753–2760.
9. Rautou P-E, Douarin L, Denninger M-H, Escolano S, Lebrec D, Moreau R, Vidaud M, Itzykson R, Moucari R, Bezeaud A, Valla D, Plessier A: Bleeding in patients with budd-chiari syndrome. J Hepatol 2011, 54(1):56–63. 10. Darwish Murad S, Valla D-C, de Groen PC, Zeitoun G, Hopmans J, Haagsma
E, Van Hoek B, Hansen B, Rosendaal F, Janssen H: Determinants of survival and the effect of portosystemic shunting in patients with budd-chiari syndrome. Hepatology 2004, 39(2):500–508.
11. McDonald GS, Gad-Al-Rab J: Behçet’s disease with endocarditis and the budd-chiari syndrome. J Clin Pathol 1980, 33(7):660–669.
12. Wilkey D, Yocum DE, Oberley TD, Sundstrom WR, Karl L: Budd-chiari syndrome and renal failure in behcet diseaseReport of a case and review of the literature. Am J Med 1983, 75(3):541–550.
13. Schattner A: Budd-chiari syndrome and renal failure in Behcet’s disease. Am J Med 1984, 77(2):A86–A91.
14. Ferraris R, Colzani G, Galatola G, Fiorentini MT: Ascites with suprahepatic portal hypertension in a case of Behçet’s disease. Panminerva Med 1985, 27(1):43–44.
15. Montagnac R, Schillinger F, Bressieux JM: Budd-chiari syndrome, an uncommon complication of Behçet’s disease. Presse Med 1986, 15(30):1427.
16. Urano Y, Ohmori H, Sugimura H, Fukushima T: Behçet’s disease with budd-chiari syndrome. Apropos of a case. Review of cases autopsied in Japan and of the literature. Ann Pathol 1986, 6(3):192–196.
17. Bismuth E, Hadengue A, Hammel P, Benhamou JP: Hepatic vein thrombosis in Behçet’s disease. Hepatology 1990, 11(6):969–974. 18. Corbella X, Casanovas T, Benasco C, Casais L: Budd-chiari syndrome
complicating Behçet’s disease. Am J Gastroenterol 1991, 86(4):526–527. 19. Saatci I, Ozmen M, Balkanci F, Akhan O, Senaati S: Behçet’s disease in the
etiology of budd-chiari disease. Angiology 1993, 44(5):392–398. 20. Danaci M, Gül S, Yazgan Y, Hülagü S, Uskent N: Budd-chiari syndrome as a
complication of Behçet’s syndrome. A case report. Angiology 1996, 47(1):93–95.
21. Oge N, Alli N: Budd-chiari syndrome as a presenting syndrome for Behçet’s disease. Int J Dermatol 1997, 36(7):556–557.
22. Bayraktar Y, Balkanci F, Bayraktar M, Calguneri M: Budd-chiari syndrome: a common complication of Behçet’s disease. Am J Gastroenterol 1997, 92(5):858–862.
23. Bayraktar Y, Ozaslan E, Van Thiel DH: Gastrointestinal manifestations of Behcet’s disease. J Clin Gastroenterol 2000, 30(2):144–154.
24. Goktekin O, Korkmaz C, Timuralp B, Kudaiberdieva G, Gorenek B, Cavusoglu Y, Melek M, Unalir A, Ata N: Widespread thrombosis associated with recurrent intracardiac masses in a patient with Behçet’s disease. Int J Cardiovasc Imaging 2002, 18(6):431–434.
25. Kuniyoshi Y, Koja K, Miyagi K, Uezu T, Yamashiro S, Arakaki K, Mabuni K, Senaha S: Surgical treatment of budd-chiari syndrome induced by Behcet’s disease. Ann Thorac Cardiovasc Surg 2002, 8(6):374–380. 26. Han SW, Kim GW, Lee J, Kim YJ, Kang YM: Successful treatment with stent
angioplasty for budd-chiari syndrome in Behçet’s disease. Rheumatol Int 2005, 25(3):234–237.
27. Korkmaz C, Kasifoglu T, Kebapçi M: Budd-chiari syndrome in the course of Behcet’s disease: clinical and laboratory analysis of four cases. Joint Bone Spine 2007, 74(3):245–248.
28. Akbaş T, Imeryüz N, Bayalan F, Baltacioglu F, Atagündüz P, Mülazimoglu L, Direskeneli H: A case of budd-chiari syndrome with Behcet’s disease and oral contraceptive usage. Rheumatol Int 2007, 28(1):83–86.
29. Seyahi E, Hamuryudan V, Hatemi G, Melikoglu M, Celik S, Fresko I, Yurdakul S, Yazici H: Infliximab in the treatment of hepatic vein thrombosis (budd-chiari syndrome) in three patients with Behcet’s syndrome. Rheumatology (Oxford) 2007, 46(7):1213–1214.
30. Ben Ghorbel I, Ennaifer R, Lamloum M, Khanfir M, Miled M, Houman MH: Budd-chiari syndrome associated with Behçet’s disease. Gastroenterol Clin Biol 2008, 32(3):316–320.
31. Carvalho DT, Oikawa FT, Matsuda NM, Evora PR, Yamada AT: Budd-chiari syndrome in a 25-year-old woman with Behçet’s disease: a case report and review of the literature. J Med Case Rep 2011, 5:52.
32. Thamotheram S, Thirumavalavan K: A case of Behcet’s disease complicated with intra cardiac thrombus and Budd chiari syndrome. Ceylon Med J 2011, 56(1):42–43.
33. Seijo S, Plessier A, Hoekstra J, Dell’era A, Mandair D, Rifai K, Trebicka J, Morard I, Lasser L, Abraldes JG, Darwish M, Heller J, Hadengue A, Primignani M, Elias E, Janssen H, Valla D, Garcia-Pagan J, European Network for Vascular Desbois et al. Orphanet Journal of Rare Diseases (2014) 9:104 Page 8 of 9
Disorders of the Liver: Good long-term outcome of budd-chiari syndrome with a step-wise management. Hepatology 2013, 57(5):1962–1968. 34. Garcia-Pagán JC, Heydtmann M, Raffa S, Plessier A, Murad S, Fabris F, Vizzini
G, Gonzales Abraldes J, Olliff S, Nicolini Lucas A, Primignani M, Janssen H, Valla D, Elias E, Bosch J, Buud-Chiari Syndrome Tranjugular Intrahepatic Portosystemic Shunt Group: TIPS for budd-chiari syndrome: long-term results and prognostics factors in 124 patients. Gastroenterology 2008, 135(3):808–815.
35. Langlet P, Escolano S, Valla D, Coste-Zeitoun D, Denie C, Mallet A, Levy VG, Franco D, Vinel JP, Belghiti J, Lebrec D, Hay JM, Zeitoun G: Clinicopathological forms and prognostic index in budd-chiari syndrome. J Hepatol 2003, 39(4):496–501.
36. Plessier A, Sibert A, Consigny Y, Hakime A, Zappa M, Denninger MH, Condat B, Farges O, Chagneau C, De Lendinghen V, Francoz C, Sauvanet A, Vilgrain V, Belghiti J, Durand F, Valla D: Aiming at minimal invasiveness as a therapeutic strategy for budd-chiari syndrome. Hepatology 2006, 44(5):1308–1316.
37. Darwish Murad S, Plessier A, Hernandez-Guerra M, Fabris F, Eapen C, Bahr M, Trebicka J, Morard I, Lasser L, Heller J, Hadengue A, Langlet P, Miranda H, Primignani M, Elias E, Leebeek F, Rosendaal F, Garcia-Pagan J, Valla D, Janssen H, European Network for Vascular Disorders of the Liver: Etiology, management, and outcome of the budd-chiari syndrome. Ann Intern Med 2009, 151(3):167–175.
38. Espinosa G, Font J, Tàssies D, Vidaller A, Deulofeu R, Lopez-Soto A, Cervera R, Ordinas A, Ingelmo M, Reverter JC: Vascular involvement in Behçet’s disease: relation with thrombophilic factors, coagulation activation, and thrombomodulin. Am J Med 2002, 112(1):37–43.
39. Leiba M, Seligsohn U, Sidi Y, Harats D, Sela BA, Griffin JH, Livneh A, Rosenberg N, Gelernter I, Gur H, Ehrenfeld M: Thrombophilic factors are not the leading cause of thrombosis in Behçet’s disease. Ann Rheum Dis 2004, 63(11):1445–1449.
40. Kim B, LeBoit PE: Histopathologic features of erythema nodosum–like lesions in behçet disease: a comparison with erythema nodosum focusing on the role of vasculitis. Am J Dermatopathol 2000, 22(5):379–390.
41. Ahn JK, Lee YS, Jeon CH, Koh E-M, Cha H-S: Treatment of venous thrombosis associated with Behcet’s disease: immunosuppressive therapy alone versus immunosuppressive therapy plus anticoagulation. Clin Rheumatol 2008, 27(2):201–205.
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